We wish to follow up on our recent finding that the antioxidant anezymes, key protectant against O2-induced lung injury, show significant increases in acitivity in fetal rabbit and rat (and human) lungs just prior to the end of normal gestation. This may have important implications for the suceptibility of the prematurely-born (human infant) to lung damange during early hyperoxic treatment. We plan to study what factors control the late fetal rise in these protective lung enzymes (hormonal? as for the surfactant system) and whether their actibity can be prematurely stimulated in the lung in utero. We wish to continue to evaluate the role of the endogenous antioxidant enzymes of the lung -- superoxide dismutase, catalase, glutathione peroxidase -- in protecting the lung from highly reacitve O2 free-radiacals produced by hyperoxia. The ability to respond to high O2 challenge with increased antioxidant enzyme activity has been shown by us to be a characteristic response in O2-tolerant newborn animals, but a long biochemical response that is lacking in O2-susceptible adult animals. The reason for this age-related disparity in lung responsiveness and sensitivity to O2-induced lung damange and lethality will be a major area to be examined. We'd like to learn why young rats lose their O2-tolerance (and ability to increase protective lung enzymjes) at around one-month of age; and whether this could be related to pubertal endocrine (sex hormone) changes and/or the (drastic) nutrional change from mother's milk (high fat-more PUFA, low CHO) to pellet diet (low fat-less PUFA, high CHO), both of which occur at around one-month of age. We also plan to study the recently found inhibitory effect of hyperoxia on normal lung growth and maturation (alveolarization) in the neonatal animal and whether pharmacological treatment can prevent this important O2 effect and its long-term sequelae. Finally, we wish to continue our preliminary development of a fetal lung culture system to more discretely analyze the effects of pharmacological agents which alter the development of the fetal lung antioxidant (and surfactant) systems. In summary, we hope to increase the understanding of why small prematures are prone to develop serious lung complications during needed O2 therapy (bronchopulmonary dysplasia); and, whether appropriate pharmacological treatment could improve their lungs capacity to resist the toxicity associated with high O2 treatment.